Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31hi Emcnhi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31hi Emcnhi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31hi Emcnhi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31hi Emcnhi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31hi Emcnhi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients\' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis.
METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions.
RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression.
CONCLUSIONS: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.

BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.
OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.
METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.
RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.
CONCLUSIONS: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.

Differential diagnosis of atypical parathyroid tumors (APT) and parathyroid carcinomas (PC) is important in determining further management and prognosis. Morphologic diagnosis is sometimes difficult, in which case it is supplemented by immunohistochemical (IHC) examination.
OBJECTIVE: Studying the role of IHC analysis in the differential diagnosis of APT and PC.
METHODS: The study included 44 patients with morphologic diagnosis of the APT established after surgical treatment for primary hyperparathyroidism on the basis of Endocrinology Research Centre during 2018-2023. All cases underwent IHC examination with evaluation of CD31/CD34 and parathormone (PTH) expression for identification of vascular invasion, Ki-67, parafibromin.
RESULTS: According to the results of IHC analysis in 8/44 patients (18.2%) the diagnosis of APT was revised in favor of the PC: in 7 of them vascular invasion was detected; in 1 patient the additional series of slices in the surrounding fatty tissue revealed foci of tumor growth, confirmed by positive reaction with antibodies to PTH. According to IHC results, the material was divided into 2 groups: APT and PC. There were no differences in clinical and morphological characteristics, Ki-67% level and parafibromin expression between the groups.
CONCLUSIONS: Assessment of clinical and laboratory-instrumental data at the preoperative stage does not allow differentiating APT from PC. In case of APT diagnosis and detection of suspicious morphological features, it is necessary to perform IHC examination to exclude PC.
Дифференциальная диагностика атипических опухолей (АО) и карцином околощитовидных желез (ОЩЖ) имеет важное значение в определении дальнейшей тактики ведения и прогноза. Морфологическая диагностика в некоторых случаях вызывает сложности, в этом случае дополняется иммуногистохимическим (ИГХ) исследованием.
UNASSIGNED: Оценить вклад ИГХ-исследования в дифференциальную диагностику АО и карцином ОЩЖ.
UNASSIGNED: В исследование включено 44 пациента с морфологическим диагнозом АО ОЩЖ, установленным после хирургического лечения по поводу первичного гиперпаратиреоза на базе ФГБУ «НМИЦ эндокринологии» Минздрава России за 2018—2023 гг. Во всех случаях было проведено ИГХ-исследование с оценкой экспрессии CD31/CD34 и паратгормона (ПТГ) для идентификации сосудистой инвазии; Ki-67, парафибромина.
UNASSIGNED: По результатам ИГХ-анализа у 8 (18,2%) из 44 пациентов диагноз АО был пересмотрен в сторону карциномы ОЩЖ: у 7 из них выявлена сосудистая инвазия, у 1 пациента при проведении дополнительной серии срезов в окружающей жировой клетчатке диагностированы очаги опухолевого роста, подтвержденные положительной реакцией с антителами к ПТГ. В соответствии с результатами ИГХ-материал был разделен на 2 группы: АО и карцинома ОЩЖ. Различий по клинико-морфологическим характеристикам, уровню Ki-67% и экспрессии парафибромина между группами не выявлено.
UNASSIGNED: Оценка клинических и лабораторно-инструментальных данных на дооперационном этапе не позволяет дифференцировать АО и карциномы. В случае диагностики АО и выявления подозрительных морфологических признаков необходимо ИГХ-исследование для исключения карциномы ОЩЖ.

BACKGROUND: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity.
METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman\'s test was used for correlation analysis. Statistical significance was set at P < .05.
RESULTS: TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/μL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/μL), with an average treatment effect of 98/μL (95% confidence interval [CI], 2-270/μL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/μL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/μL), with an average treatment effect (ATE) of 79/μL (95% CI, 19-171/μL); these EDEV levels remained elevated until day 5.
CONCLUSIONS: EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

The cardiac perivascular niche is a cellular microenvironment of a blood vessel. The principles of niche regulation are still poorly understood. We studied the effect of TGFβ1 on cells forming the cardiac perivascular niche using 3D cell culture (cardiospheres). Cardiospheres contained progenitor (c-Kit), endothelial (CD31), and mural (αSMA) cells, basement membrane proteins (laminin) and extracellular matrix proteins (collagen I, fibronectin). TGFβ1 treatment decreased the length of CD31+ microvasculature, VE cadherin protein level, and proportion of NG2+ cells, and increased proportion of αSMA+ cells and transgelin/SM22α protein level. We supposed that this effect is related to the stabilizing function of TGFβ1 on vascular cells: decreased endothelial cell proliferation, as shown for HUVEC, and activation of mural cell differentiation.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of βIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of \"Zusanli\"(ST36) and\"Xuehai\"(SP10) on the angiogenesis of the local injured skin tissue in mice with psoriasis, so as to explore its mechanisms underlying improvement of psoriasis-induced skin lesions.
METHODS: A total of 24 female BALB/c mice aged 6-8 weeks were randomly divided into control, model and EA groups, with 8 mice in each group. The psoriasis-like skin lesion model was established by application of 5% imiquimod (IMQ) cream to the mice\'s back skin, 62.5 mg/d, for 7 days after local depilation, and the mice of the control group received local application of an equal amount of petroleum jelly once a day for 7 days. EA stimulation (2 Hz/100 Hz) was applied to ST36 and SP10 for 30 min, once daily for 7 consecutive days. Photos of the topical injured skin at the back were taken every day, and the severity of psoriasis lesions (psoriasis area and severity index ［PASI］) was scaled. Following H.E. staining, the morphological changes in the injured skin tissue were observed with epidermal thickness analyzed, and the Masson staining was used to observe the proportion of collagen fibers in the injured skin tissues. Immunohistochemical method was used to detect the expression of microvascular markers CD31 and vascular endothelial growth factor (VEGF) and the microvascular density (MVD) was calculated. Western blot was used to detect the expression levels of CD31, VEGF proteins and mitogen activated protein kinases (MAPK) signaling pathway related proteins p38, phosphorylated p38 (p-p38), extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK) and p-JNK in the injured skin tissue.
RESULTS: Compared with the control group, the mice in the model group showed an evident increase in the erythema score, scales score, skin thickening score and PASI score, epidermal thickness, proportion of the collagen fibers, MVD value of CD31 and VEGF, and expression levels of CD31 and VEGF proteins, and p-p38/p38, p-ERK/ERK and p-JNK/JNK ratios in the injured skin tissue (P<0.001, P<0.01). In contrast to the model group, the EA group had a significant decrease in the levels of all the indexes mentioned above (P<0.05, P<0.01, P<0.001).
CONCLUSIONS: EA intervention can improve the psoriasis-like skin lesions induced by IMQ in mice, which may be related with its functions in down-regulating the expression of angiogenic related factors CD31 and VEGF proteins and MAPK signaling pathway related proteins in the topical injured skin tissue.
目的: 观察电针“足三里”“血海”对咪喹莫特（IMQ）诱导的小鼠银屑病皮损组织血管生成的影响，探讨电针缓解银屑病皮损的机制。方法: 选取24只雌性BALB/c小鼠，随机分为空白对照组、模型组、电针组，每组8只。模型组、电针组小鼠用5% IMQ乳膏对其背部皮肤进行涂抹以诱导银屑病模型；电针组小鼠在造模同时给予电针双侧“足三里”“血海”，1次/d，30 min/次，连续7 d。每天对小鼠背部皮损处皮肤拍照，采用银屑病面积和严重程度指数（PASI）进行评分，观察小鼠皮损动态变化；HE染色观察皮损组织形态学变化、表皮厚度及炎性细胞浸润程度；Masson染色观察并计算皮损组织胶原纤维占比；免疫组织化学法检测皮损组织微血管标志物CD31、血管内皮生长因子（VEGF）的阳性表达并计算微血管密度（MVD）；Western blot法检测皮损组织中CD31、VEGF及丝裂原活化蛋白激酶（MAPK）信号通路相关蛋白p38、磷酸化（p）-p38、细胞外调节蛋白激酶（ERK）、p-ERK、c-Jun氨基末端激酶（JNK）、p-JNK的表达水平。结果: 与空白对照组相比，模型组小鼠背部皮肤出现红斑、鳞屑、皮肤增厚症状，第7天红斑、鳞屑、皮肤增厚程度评分及总PASI评分升高（P<0.001），表皮明显增厚（P<0.001），胶原纤维占比、皮肤组织CD31及VEGF的MVD值、皮肤组织CD31、VEGF的蛋白表达水平及MAPK信号通路相关蛋白p-p38/p38、p-ERK/ERK、p-JNK/JNK比值明显升高（P<0.001，P<0.01）。与模型组相比，电针组小鼠背部皮损明显改善，第7天红斑、鳞屑、皮肤增厚程度评分及总PASI评分显著下降（P<0.05，P<0.01），表皮厚度明显降低（P<0.001），皮损组织胶原纤维占比明显减少（P<0.01），皮损组织CD31、VEGF的MVD值、皮损组织CD31、VEGF的蛋白表达水平及MAPK信号通路相关蛋白p-p38/p38、p-ERK/ERK、p-JNK/JNK比值明显降低（P<0.05，P<0.001，P<0.01）。结论: 电针“足三里”“血海”可改善IMQ诱导的小鼠银屑病样皮损改变，其作用机制可能是通过调控MAPK信号通路抑制皮损处血管生成相关因子CD31和VEGF的表达，从而改善银屑病皮损症状。.

BACKGROUND: Contrast enhancement of intracranial aneurysm wall during MRI with targeted visualization of vascular wall correlates with previous aneurysm rupture and, according to some data, may be a predictor of further rupture of unruptured aneurysms.
OBJECTIVE: To analyze possible causes of aneurysm contrast enhancement considering morphological data of aneurysm walls.
METHODS: The study included 44 patients with intracranial aneurysms who underwent preoperative MRI between November 2020 and September 2022. Each aneurysm was assessed regarding contrast enhancement pattern. Microsurgical treatment of aneurysm was accompanied by resection of its wall for subsequent histological and immunohistochemical analysis regarding thrombosis, inflammation and neovascularization. Specimens were subjected to histological and immunochemical analysis. Immunohistochemical analysis was valuable to estimate inflammatory markers CD68 and CD3, as well as neurovascularization marker SD31.
RESULTS: Aneurysms with contrast-enhanced walls were characterized by higher number of CD3+, CD68+, CD31+ cells and parietal clots. Intensity of contrast enhancement correlated with aneurysm wall abnormalities.
CONCLUSIONS: Contrast enhancement of aneurysm wall can characterize various morphological abnormalities.
Накопление контрастного препарата в стенке интракраниальной аневризмы при проведении магнитно-резонансной томографии (МРТ) с контрастным усилением и прицельной визуализацией сосудистой стенки коррелирует с наличием ранее имевшегося разрыва аневризмы и, по некоторым данным, может служить предиктором разрыва неразорвавшихся аневризм.
UNASSIGNED: Определить возможные причины контрастирования стенки аневризмы при МРТ-сканировании на основании морфологических исследований стенок аневризм.
UNASSIGNED: В исследование включены 44 пациента с интракраниальными аневризмами, которым проводилась дооперационная МРТ по специальному протоколу на аппарате 3 Тл в период с ноября 2020 г. по сентябрь 2022 г. Каждая аневризма оценивалась на наличие контрастирования и интенсивность контрастирования стенки. В ходе микрохиругического выключения аневризм проводилась резекция ее стенки для последующего гистологического и иммуногистохимического исследования с определением наличия тромбоза, воспаления и неоваскуляризации. Биопсийный материал исследовали гистологически и иммуногистохимически. При иммуногистохимическом исследовании определяли маркеры воспаления CD68, CD3 и маркеры неоваскуляризации CD31.
UNASSIGNED: В аневризмах, стенка которых накапливала контрастный препарат, были обнаружены увеличение CD3+, CD68+, CD31+-клеток и пристеночные тромботические массы. Интенсивность накопления контрастного препарата при МР-исследовании коррелировала с патологическими изменениями в стенке аневризмы.
UNASSIGNED: Накопление контрастного препарата в сосудистой стенке и его интенсивность могут отражать характер изменений в ней.